Background: The United States (US) ranks high, nationally, in opioid consumption. The ongoing increase in the misuse and mortality amid the opioid epidemic has been contributing to its rising cost. The worsening health and economic impact of opioid use disorder in the US warrants further attention. We, therefore, assessed commonly prescribed opioids to determine the opioids that were over-represented versus under-represented for adverse drug events (ADEs) to better understand their distribution patterns using the Food and Drug Administration’s Adverse Event Reporting System (FAERS) while correcting for distribution using the Drug Enforcement Administration’s Automation of Reports and Consolidated Orders System (ARCOS). Comparing the ratio of the percentage of adverse drug events as reported by the FAERS relative to the percentage of distribution as reported by the ARCOS database is a novel approach to evaluate post-marketing safety surveillance and may inform healthcare policies and providers to better regulate the use of these opioids.Methods: We analyzed the adverse events for 11 prescription opioids, when correcting for distribution, and their ratios for three periods, 2006–2010, 2011–2016, and 2017–2021, in the US. The opioids include buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, and tapentadol. Oral morphine milligram equivalents (MMEs) were calculated by conversions relative to morphine. The relative ADEs of the selected opioids, opioid distributions, and ADEs relative to distribution ratios were analyzed for the 11 opioids.Results: Oxycodone, fentanyl, and morphine accounted for over half of the total number of ADEs (n = 667,969), while meperidine accounted for less than 1%. Opioid distributions were relatively constant over time, with methadone repeatedly accounting for the largest proportions. Many ADE-to-opioid distribution ratios increased over time, with meperidine (60.6), oxymorphone (11.1), tapentadol (10.3), and hydromorphone (7.9) being the most over-represented for ADEs in the most recent period. Methadone was under-represented (<0.20) in all the three periods.Conclusion: The use of the FAERS with the ARCOS provides insights into dynamic changes in ADEs of the selected opioids in the US. There is further need to monitor and address the ADEs of these drugs.

The United States (US) is going through an opioid crisis with annual increases in opioid-related mortality. Our study analyzed the adverse drugs events (ADEs) for eleven prescription opioids when correcting for distribution, and their ratios for three periods: 2006-2010, 2011-2016, and 2017-2021 in the US. The opioids included buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, and tapentadol. The Food and Drug Administration Adverse Event Reporting System (FAERS) database consists of reports by MedWatch adverse event forms submitted by healthcare professionals and others (N=667,969), whereas the Automation of Reports and Consolidated Orders System (ARCOS) reports on medically used controlled substances. Oral morphine milligram equivalents (MMEs) were calculated by conversion relative to morphine. The relative ADEs of the select opioids calculated from FAERs, opioid distribution from ARCOS, and the FAERs to ARCOS ratios were analyzed for the eleven opioids. Oxycodone reports peaked in the third period and showed consistently high ADEs. Codeine and meperidine accounted less than five percent of ADEs. The ARCOS distributions were relatively constant over time, but methadone consistently accounted for the largest portion of the total distribution. The FAERS to ARCOS ratios generally increased over time, with meperidine (60.6), oxymorphone (11.1), tapentadol 10.3, and hydromorphone (7.9) most over-represented for ADEs in the third period. Oxymorphone had a 542.2% increase in ratio between the second and third period should be noted. Methadone was under-represented (< .20) in all three periods. These findings indicate the need to further monitor and address the ADEs of select opioids.SignificancePrescription opioid use in the US is among the highest in the world. This study analyzed both FAERs and ARCOS databases to understand the adverse drugs events. This investigation identified which opioids were overrepresented (e.g. meperidine) and underrepresented (e.g. methadone) for adverse effects relative to the prevalence of use to inform healthcare policies and change the way physicians view and prescribe these opioids.

Introduction: Dronabinol is approved in the USA for chemotherapy-induced nausea as well as vomiting and HIV-induced anorexia, while cannabidiol is primarily approved for childhood epileptic disorders Lennox-Gastaut and Dravet syndrome. The use pattern for these prescription cannabinoids in the USA is unknown. This study examined Medicaid claims for two FDA-approved prescription cannabinoids, dronabinol and cannabidiol, approved in 1985 and 2018, respectively, from 2016–2020 to better understand the pharmacoepidemiologic trends and distribution of these drugs in US Medicaid amidst the increasing use of non-pharmaceutical formulations of cannabis. Methods: The longitudinal study analyzed Medicaid prescription claims that were calculated by extracting the prescriptions on a state level from 2016 to 2020 for two cannabinoids, dronabinol and cannabidiol, where outcomes over each year were calculated. Outcomes were (1) the number of prescriptions for each state corrected for the number of Medicaid enrollees and (2) dronabinol and cannabidiol spending. Spending refers to the amount reimbursed by the state Medicaid program. Results: Dronabinol prescriptions per state decreased by 25.3% from 2016 to 2020, while cannabidiol prescriptions increased by 16,272.99% from 2018 to 2020. The spending on these drugs parallels that of their prescription trend with a 66.3% decrease in reimbursement for dronabinol ($5.7 million in 2020), whereas cannabidiol increased by +26,582.0% ($233.3 million in 2020). Dronabinol prescriptions, when corrected for the number of enrollees, in Connecticut were 136.4 times larger than in New Mexico, and seventeen states had zero prescriptions. Idaho’s prescriptions of cannabidiol (27.8/10,000 enrollees) were significantly elevated relative to the national average and were 15.4-fold higher than Washington, DC (1.8/10K enrollees). Conclusions: The prescriptions of pharmaceutical-grade tetrahydrocannabinol decreased while those of cannabidiol increased. This study also identified pronounced state-level variation in cannabinoid prescribing to Medicaid patients. State formularies and prescription drug list variation may contribute to the drug reimbursements in Medicaid, though further research is needed to identify the health policy or pharmacoeconomic origins of these disparities.

Background: Dronabinol is approved for chemotherapy induced nausea as well as vomiting and HIV-induced anorexia, while cannabidiol is primarily approved for childhood epileptic disorders Lennox-Gastaut and Dravet syndrome. The use pattern for these prescription cannabinoids in the US is unknown. Methods: This study analyzed Medicaid claims and spending for dronabinol and cannabidiol prescriptions from 2016-2020. Results: Dronabinol prescriptions decreased by 25.3% from 2016 to 2020 while cannabidiol prescriptions increased by 16,272.99 % from 2018 to 2020. The spending on these drugs parallels that on their prescription trend with a 66.3% decrease in reimbursement for dronabinol ($5.7 million in 2020), whereas that of cannabidiol increased by +26,582.0% ($233.3 million in 2020). Dronabinol prescriptions in Connecticut were 136.4 times larger than New Mexico and 17 states had zero prescriptions. Idaho prescriptions, when corrected for number of enrollees, were 15.4-fold higher than Washington DC. Prescribing of dronabinol and cannabidiol did not differ significantly based on the whether the state had an active medical marijuana program. Conclusions: The prescriptions of pharmaceutical grade tetrahydrocannabinol were decreasing while cannabidiol was increasing. This study also identified pronounced state level variation in cannabinoid prescribing to Medicaid patients. Further research to identify the origins of these disparities is needed.